The overall objectives of this project are to characterize in functional terms the antigen-sensitive cell populations in the intestine, to define the pathways by which intestinal antigen-sensitive cells can be induced by antigen to express humoral and cell-mediated effector functions, and to examine the potential relevance of immune effector mechanisms in the pathogenesis of immune tissue injury in the intestine. Murine Peyer's patches contain antigen-sensitive B and T cells but are naturally deficient in an accessory adherent cell type(s) required in vitro for the induction of both humoral antibody synthesis and cell-mediated cytotoxic reactions. We have demonstrated that T cells in murine Peyer's patches can be carrier-primed for helper function in the induction of an anti-hapten response by feeding antigen. In contrast, we have been unable to demonstrate T cells in Peyer's patches capable of antigen-specific, hapten-specific or nonspecific suppression of the B cell response. Limiting dilution analysis indicated that the frequency of antigen-sensitive B cells which can respond to a specific antigen was similar in Peyer's patches and the spleen but the number of antibody-forming cells produced by each responding Peyer's patch B cell following antigenic encounter was significantly greater. These findings are consistent with prior studies from this laboratory which suggested that B cells in Peyer's patches comprise a more differentiated population than B cells in extraintestinal sites such as the spleen. Studies to examine killing of coated and uncoated erythrocyte target cells by an antibody-dependent cell-mediated cytotoxic mechanism (ADCC) indicated that Peyer's patches lack the cell type required to kill erythrocyte target cells. Moreover Peyer's patches do not contain a population of cells capable of mediating ADCC killing via the lgA class. Finally, we developed a system for assaying ADCC of cultured adherent human colon cancer cells and have demonstrated that human colon cancer cells in vitro can be killed by an ADCC mechanism. BIBLIOGRAPHIC REFERENCES: Kagnoff, M.F. and Campbell, S. Antibody-dependent cell-mediated cytotoxicity: comparative ability of murine Peyer's patch and spleen cells to lyse lipopolysaccharide-coated and uncoated erythrocytes. Gastroenterology, in press, March, 1976.